Matti Härkönen

Lipoprotein lipase activity in adipose tissue and skeletal muscle of runners: Relation to serum lipoproteins

Physically well-trained people generally have lower VLDL-triglyceride and higher HDL-cholesterol levels than sedentary subjects. To examine the underlying mechanisms of this lipoprotein pattern, we measured the lipoprotein lipase (LPL) activity in needle biopsy specimens of adipose tissue and skeletal muscle of competitive runners and of body weight-matched, physically less-active controls. The active sportsmen were either sprinters, whose training program consisted mainly of athletics of short duration or long distance runners undergoing a strenuous endurance exercise program. In sprinters (all males) the serum lipid and lipoprotein concentrations did not differ significantly from those of controls and the mean LPL activities in muscle and adipose tissue were also similar in these two groups. The long distance runners (both sexes), on the other hand, had higher means levels of HDL-cholesterol than the respective controls. The LPL-activity of both adipose tissue (p less than 0.05) and skeletal muscle (p less than 0.01) was significantly higher in male long distance runners than in control males. Female runners had higher muscle LPL activity than controls (p less than 0.01) but in adipose tissue the difference in LPL activity was not significant. Rough estimates calculated for LPL activity present in whole body adipose tissue and skeletal muscle indicated that total LPL activity was 2.3 times higher in male long distance runners and 1.5 times higher in female long distance runners than in the respective controls. In combined groups of male runners and controls, there was a highly significant positive correlation between the serum HDL-cholesterol level and the LPL activity of adipose tissue expressed per tissue weight (r = +0.72, p less than 0.001) or per whole body fat (r = +0.62, p less than 0.001). The group means of HDL-cholesterol and adipose tissue LPL activity in the five cohorts studied (male sprinters, distance runners and controls and female distance runners and controls) were also positively correlated (r = +0.94). It is concluded that endurance training is associated with an adaptive increase of LPL activity not only in skeletal muscle but also in adipose tissue. These changes are not observed in sprinters who are trained by exercises of shorter duration. The high HDL-cholesterol levels of physically well-trained people are probably accounted for, at least partly, by the increased LPL activity and the concomitant rapid turnover or triglyceride-rich lipoproteins.

Breakdown of high-energy phosphate compounds and lactate accumulation during short supramaximal exercise.

SummaryMuscle ATP, creatine phosphate and lactate, and blood pH and lactate were measured in 7 male sprinters before and after running 40, 60, 80 and 100 m at maximal speed. The sprinters were divided into two groups, group 1 being sprinters who achieved a higher maximal speed (10.07±0.13 m ·s−1) than group 2 (9.75±0.10 m ·s−1), and who also maintained the speed for a longer time. The breakdown of high-energy phosphate stores was significantly greater for group 1 than for group 2 for all distances other than 100 m; the breakdown of creatine phosphate for group 1 was almost the same for 40 m as for 100 m. Muscle and blood lactate began to accumulate during the 40 m exercise. The accumulation of blood lactate was linear (0.55±0.02 mmol · s−1 ·1−1) for all distances, and there were no differences between the groups. With 100 m sprints the end-levels of blood and muscle lactate were not high enough and the change in blood pH was not great enough for one to accept that lactate accumulation is responsible for the decrease in running speed over this distance.We concluded that 1) in short-term maximal exercise, performance depends on the capacity for using high-energy phosphates at the beginning of the exercise, and 2) the decrease in running speed begins when the high-energy phosphate stores are depleted and most of the energy must then be produced by glycolysis.

The effect of Simvastatin treatment on natural antioxidants in low-density lipoproteins and high-energy phosphates and ubiquinone in skeletal muscle*

It has been hypothesized that treating hypercholesterolemic patients with statins will lead not only to a reduction in cholesterol, but also to inhibited synthesis of other compounds which derive from the synthetic pathway of cholesterol. In theory, this could further lead to ubiquinone deficiency in muscle cell mitochondria, disturbing normal cellular respiration and causing adverse effects such as rhabdomyolysis. Furthermore, ubiquinone is one of the lipophilic antioxidants in low-density lipoprotein (LDL), and therefore it has also been hypothesized that statin treatment will reduce the antioxidant capacity of LDL. We investigated the effect of 6 months of simvastatin treatment (20 mg/day) on skeletal muscle concentrations of high-energy phosphates and ubiquinone by performing biopsies in 19 hypercholesterolemic patients. Parallel assays were performed in untreated control subjects. The muscle high-energy phosphate and ubiquinone concentrations assayed after simvastatin treatment were similar to those observed at baseline and did not differ from the values obtained in control subjects at the beginning and end of follow-up. These results do not support the hypothesis of diminished isoprenoid synthesis or energy generation in muscle cells during simvastatin treatment. Furthermore, the results of analysis of antioxidant concentrations in LDL before and after simvastatin treatment indicate that the antioxidant capacity of LDL is maintained in simvastatin-treated patients.

Plasma cortisol, androstenedione, testosterone and luteinizing hormone in running exercise of different intensities

Changes in plasma cortisol, androstenedione, testosterone and luteinizing hormone (LH) were measured in five young male sprinters after maximal short-term running and in five young male long-distance runners after moderate (90 min, 4.3 min/km) and intense (45 min, 3.3 min/km) long-term running. Short-term running increased mean plasma cortisol (27%) and androstenedione (19%) significantly; no appreciable changes were found in mean plasma testosterone or LH levels. Intense long-term running caused considerable increases in mean plasma cortisol (43%) and androstenedione (53%). Immediately after the long-term runs mean plasma testosterone and LH did not show nay significant changes, but half an hour later mean plasma LH was found to have dropped significantly below the preceding level, by 42% after the moderate run and by 45% after the intense run. At this time the intense long-term run caused a significant decrease in mean plasma testosterone, which remained depressed up to 3 h after the end of the exercise. This study implies that the changes in plasma hormone levels depend more on the intensity of the exercise than on its duration. The activity of the pituitary-adrenocortical system appears to be a good indicator of the effort expended during the exercise. In the pituitary-testicular system, in contrast, the effort expended may be more accurately reflected by changes during the recovery period.

Effect of strenuous anaerobic running exercise on plasma growth hormone, cortisol, luteinizing hormone, testosterone, androstenedione, estrone and estradiol

Abstract Plasma growth hormone (GH), cortisol, luteinizing hormone (lutropin, LH), testosterone, androstenedione, estrone and estradiol levels were investigated before and after strenuous anaerobic running exercise of short duration in five male runners. After the exercise there were statistically significant increases in the mean plasma concentrations of GH (233%), LH (49%), testosterone (13%) and androstenedione (34%). Plasma cortisol increased only slightly. The testosterone and androstenedione concentrations in the samples taken 6 h after exercise were below the control levels (51 and 40%, respectively). This effect was more pronounced than during the day of normal activity when in the same subjects the testosterone concentration decreased only 12%, and the androstenedione concentration did not change at all. Exercise affected plasma estradiol levels in the same way as it did testosterone and estrone levels in the same way as cortisol. Control values were not reattained for some of the hormones until more than 24 h after the run. In this study the most fit runner showed greater LH, testosterone, androstenedione and cortisol response than the least fit runner, who had a more elevated GH level after the run.

Spontaneous disappearance of Helicobacter pylori antibodies in patients with advanced atrophic corpus gastritis

Background. Only a few reported studies focus on the natural history and course of advanced and severe chronic atrophic gastritis. Methods. In this study we followed 47 men (mean age 62 years) with advanced (moderate or severe) Helicobacter pylori‐positive atrophic corpus gastritis. Duration of endoscopic follow‐up was 6 years and follow‐up based on serum levels of pepsinogen I and antibodies to H. pylori covered a period of 10 years. None of the patients was treated for H. pylori infection prior to end of follow‐up. Results. The median H. pylori antibody titre declined (IgG from 4000 to 1300; IgA from 200 to 50) in the study population, and 11 men (23%) converted to seronegative (p=0.0005, Fishers exact test). There was a small but significant (p=0.0004, Pages test) declining trend in mean atrophy score of the corpus during follow‐up (from 2.5 to 2.2). However, no significant changes were observed in grade of atrophy or intestinal metaplasia of the antral mucosa or in grade of intestinal metaplasia in the corpus. The mean SPGI level remained at the initial low level during the entire follow‐up. Conclusions. H. pylori antibodies disappear spontaneously within 10 years in almost one fourth of patients with advanced atrophic corpus gastritis. The disappearance of H. pylori antibodies is accompanied by no or more than a mild improvement of the gastric mucosa.

Serum levels of amidated gastrin-17 and pepsinogen I in atrophic gastritis: An observational case-control study

Background: Helicobacter pylori infection is often diagnosed with non-endoscopic methods, such as serology or breath or antigen stool tests. These tests provide information on the presence or absence of the H. pylori gastritis only. We investigated whether atrophic gastritis can be diagnosed and typed nonendoscopically if the serum levels of pepsinogen I (S-PGI) and gastrin-17 (S-G-17) are assayed in connection with H. pylori testing. Methods: The present investigation is an observational case-control study comprising 100 selected dyspeptic outpatients with (cases) or without (controls) advanced (moderate or severe) atrophic gastritis. Before the blood tests, all patients underwent a diagnostic gastroscopy with multiple biopsies. The series of cases includes 56 patients. Eight had an advanced antrum limited atrophic gastritis, 13 had resected antrum (in two of whom the corpus mucosa in the stump was atrophic), and 30 had corpus-limited atrophic gastritis. Four patients had an advanced atrophic gastritis in both the antrum and corpus (multifocal atrophic gastritis), and the whole stomach was removed in one patient. Twenty of the 44 controls had a non-atrophic H. pylori gastritis. Both the antrum and corpus were normal and healthy in 24 patients. The S-PGI and S-G-17 were determined with EIA methods using monoclonal antibodies to PGI and amidated G-17. Postprandial S-G-17 (S-G-17prand) was measured 20 min after a protein-rich drink. The H. pylori antibodies were assayed with a polyclonal EIA method. Results: A low S-PGI (<25 μg/l; an empirical cut-off with best discrimination) was found in 31 of 37 patients (84%) with and in 3 of 63 patients (5%) without corpus atrophy in the biopsy specimens. A low S-G-17prand (<5 pmol/l) was found in all 8 patients with H. pylori -associated antral atrophy and in 11 of 14 patients (79%) with resected antrum but in 3 of 20 control patients (15%) with H. pylori -related non-atrophic gastritis. Median and mean values of both S-G-17prand and S-PGI decreased with increasing grade of antral and corpus atrophy, respectively. Among all patients with atrophic gastritis (multifocal atrophic gastritis, or atrophic gastritis limited to antrum or corpus) or resected stomach, 50 of 56 patients (89%; CI 95%: 81%-97%) had a low SPGI and/or a low S-G-17prand with positive H. pylori serology. Such low values were found in 3 of the 44 control patients (7%; CI 95%: 0%-14%). Conclusions: Low serum levels of G-17prand and PGI are conceivable biomarkers of atrophic antral and corpus gastritis, respectively. A low S-G-17prand is a sign of the multifocal or antrum-limited atrophic gastritis in patients infected with H. pylori .

The effect of Helicobacter pylori eradication on the natural course of atrophic gastritis with dysplasia

There are few data on the natural course of Helicobacter pylori‐related atrophic gastritis.

Implications of Serum Pepsinogen I in Early Endoscopic Diagnosis of Gastric Cancer and Dysplasia

K. Varis, P. Sipponen, F. Laxén, I. M. Samloff, J. K. Huttunen, P. R. Taylor, O. P. Heinonen, D. Albanes, N. Sande, J. Virtamo, M. Härkönen & the Helsinki Gastritis Study Group* National Public Health Institute; Dept. of Public Health, University of Helsinki; and Dept. of Clinical Chemistry, Helsinki University Central Hospital; Helsinki, and Jorvi Hospital, Espoo, Finland, and V. A. Medical Center, Sepulveda, California, and National Cancer Institute, Bethesda, Maryland, USA

Bone mineral density and abstention-induced changes in bone and mineral metabolism in noncirrhotic male alcoholics

BACKGROUND AND PURPOSE Abuse of alcohol may derange bone metabolism and cause osteoporosis. Due to confounding factors associated with alcohol abuse, however, the effect of alcohol itself on bone loss remains obscure. The influence of alcohol intake on bone and mineral metabolism is rather well known, but how the metabolism normalizes during withdrawal has rarely been investigated. The aims of the present study were to evaluate the alcohol-induced changes of bone and mineral metabolism and their recovery during abstention, and to reassess any possible link between alcohol abuse and osteoporosis. PATIENTS AND METHODS We studied 27 non-cirrhotic male alcoholics hospitalized for 2 weeks for withdrawal. For comparison, three groups of control subjects were examined. Serum and urinary parameters of bone and mineral metabolism as well as intestinal absorption of calcium were determined at the beginning and end of the treatment period. Bone mineral density (BMD) was measured by dual-energy x-ray absorptiometry at four axial sites (lumbar spine, femoral neck, Wards triangle, trochanter). RESULTS On admission, bone formation in the alcoholics was reduced as reflected by decreased serum levels of osteocalcin (-28%; p < 0.05) and procollagen I carboxyterminal propeptide (-17%; p < 0.05). Both parameters normalized within 2 weeks of abstention (p < 0.0001 and p < 0.01, respectively). Urinary hydroxyproline, a parameter of bone resorption, was at the control level on admission and increased slightly during abstention (p < 0.05). Serum ionized calcium increased by 3% (p < 0.0001) during withdrawal. Concomitantly, serum free fatty acids (FFA) decreased by 38% (p < 0.001), and there existed an inverse correlation (r = -0.50, p < 0.05) between changes in ionized calcium and FFA. Serum levels of intact parathyroid hormone and vitamin D metabolites were similar in patients and controls throughout the whole observation period. Intestinal absorption of calcium measured by stable strontium was 37% higher in alcoholics than in controls (p < 0.001); it decreased to nearly normal toward the end of the treatment period. Mean axial BMD did not differ between patients and controls at any of the four measurement sites. However, BMD decreased parallel with duration of drinking history in the alcoholics at all axial sites (p < 0.05 to < 0.01, analysis of covariance with age and weight as covariates). CONCLUSIONS Decreased bone formation, which is uncoupled from ongoing bone resorption, recovers completely during 2 weeks of abstention. In the absence of confounding factors, the central BMD is normal in noncirrhotic male alcoholics, although the negative effect of alcohol on BMD is evident when duration of excessive drinking is taken into account.